The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern

Authors

  • Thiru Prasanna Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
  • Christos S. Karapetis Department of Medical Oncology, Flinders Medical Centre, Bedford Park, Australia; ;Flinders Clinical and Molecular Medicine, Surgery, Flinders University, Bedford Park, Australia
  • David Roder South Australian Health & Medical Research Institute (SAHMRI), Adelaide, Australia; ;School of Health Sciences, University of South Australia, Adelaide, Australia
  • Jeanne Tie Department of Medical Oncology, Western Hospital, Melbourne, Australia; ;Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; ;Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
  • Robert Padbury Padbury Flinders Clinical and Molecular Medicine, Surgery, Flinders University, Bedford Park, Australia; ;Department of Surgery, Flinders Medical Centre, Adelaide, Australia
  • Timothy Price The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia
  • Rachel Wong Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; ;Department of Medical Oncology, Eastern Health, Melbourne, Australia; ;Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
  • Jeremy Shapiro Cabrini Haematology and Oncology Centre, Melbourne, Australia
  • Louise Nott Department of Medical Oncology, Royal Hobart Hospital, Tasmania, Australia; ;Menzies Research Institute, Hobart, Australia
  • Margaret Lee Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; ;Department of Medical Oncology, Eastern Health, Melbourne, Australia; ;Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
  • Yu Jo Chua Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia; ;ANU Medical School, Australian National University, Canberra, Australia
  • Paul Craft Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia; ;ANU Medical School, Australian National University, Canberra, Australia
  • Cynthia Piantadosi Flinders Centre for Innovation in Cancer, Bedford Park, Australia
  • Michael Sorich College of Medicine and Public Health, Flinders University, Adelaide, Australia
  • Peter Gibbs Department of Medical Oncology, Western Hospital, Melbourne, Australia; ;Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
  • Desmond Yip Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia; ;ANU Medical School, Australian National University, Canberra, Australia

DOI:

https://doi.org/10.1080/0284186X.2018.1487581

Abstract

Background: Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis.

Methods: Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel–Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics.

Results: Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01).

Conclusion: Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.

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Published

2018-12-02

How to Cite

Prasanna, T. ., Karapetis, C. S. ., Roder, D. ., Tie, J. ., Padbury, R. P., Price, T., … Yip, D. . (2018). The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern. Acta Oncologica, 57(11), 1438–1444. https://doi.org/10.1080/0284186X.2018.1487581

Issue

Vol. 57 No. 11 (2018): Acta Oncologica

Section

Articles